Synthetic biology aims to engineer genetically modified biological systems that perform novel functions that do not exist in nature, with reusable, standard interchangeable biological parts. The use of these standard biological parts enables the exploitation of common engineering principles such as standardization, decoupling, and abstraction for synthetic biology. With this engineering framework in place, synthetic biology has the potential to make the construction of novel biological systems a predictable, reliable, systematic process. While the development of most synthetic biological systems remains largely ad hoc, recent efforts to implement an engineering framework in synthetic biology have provided long-awaited evidences that engineering principles can facilitate the construction of novel biological systems. Synthetic biology has demonstrated that its framework can be applied to a wide range of areas such as energy, environment, and health care. For example, biological systems have been constructed to produce drugs and biofuels, to degrade contaminants in water, and to kill cancer cells.
Despite these advances, synthetic biology has not yet been exploited to develop new strategies for tackling infectious disease, a leading cause of death worldwide, especially in poor countries. Given the stalled development of new antibiotics and the increasing emergence of multidrug-resistant pathogens, using synthetic biology to design new treatment regimens for infectious disease could address an urgent need.
Pseudomonas aeruginosa (or often referred to as P. aeruginosa) colonizes the respiratory and gastrointestinal tract, and causes life-threatening infections to patients with immunodeficiency such as cystic fibrosis and cancer. Despite a wide range of antibiotics available in the market, P. aeruginosa is still among the leading causes of nosocomial infection primarily because it is intrinsically resistant to many antibiotics and antimicrobials, in part because of its effective efflux systems. Contemporary treatments against P. aeruginosa infection include antibiotic chemotherapy and bacteriophage therapy. In antibiotic chemotherapy, a combinatorial treatment involving multiple antimicrobial agents is usually preferred over monotherapy due to the rapid acquisition of drug tolerance in P. aeruginosa. This approach, however, promotes unspecific killing of bacteria and upsets a healthy human microbiome. Phage therapy involves strain-specific bacteriophages that invade and destroy the cellular integrity of pathogens. The therapeutic potential of employing virus in bacterial infection, however, is limited, as a directed treatment cannot be re-employed after the infected host develops specific antibodies against the introduced virus.
Thus, there is need in the art for novel, unconventional antimicrobial strategies that do not entirely rely on current antibiotics that address the problems mentioned above, especially in combating P. aeruginosa infections.